Molecular and functional characterization of endocrine-metabolic, cardiovascular and neurological changes in the double burden of malnutrition: Potential mechanisms of action of Tauroursodeoxycholic Acid (TUDCA)

• Grant number: 24/23120-6
• Support Opportunities: Research Projects - Thematic Grants
• Start date: November 01, 2025
• End date: October 31, 2030
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Everardo Magalhães Carneiro
• Grantee: Everardo Magalhães Carneiro
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Pesquisadores principais: Ana Paula Couto Davel
• Associated researchers: Alejandro Caicedo ; Alex Rafacho ; Aline Mara dos Santos ; Angel Nadal ; Bruno Geloneze Neto ; Gabriela Moreira Soares ; Helena Cristina de Lima Barbosa ; Ivan Quesada ; Lígia de Moraes Antunes Corrêa ; Nathalia Romanelli Vicente Dragano

Abstract

The growth in the number of obese people in underdeveloped and developing countries has led to the emergence of overweight and obesity in previously undernourished individuals, giving rise to the phenomenon of double burden of malnutrition (DCM). It is known, since the economic phenotype hypothesis, that changes in the quality and quantity of nutrients during the early stages of life can compromise the function of various tissues to prioritize the development of organs essential to body homeostasis. This makes the body more susceptible to the development of diseases such as obesity, diabetes, cardiovascular and neurological damage in adult life. Therefore, it is believed that DCM can lead to health problems differently from obesity without prior malnutrition. In rodents, it has been shown that DCM leads to greater susceptibility to body weight gain and obesity, compromised endocrine function of the pancreas and increased risk for the development of diabetes. However, the repercussions in relation to cardiovascular, neurological and endocrine-metabolic functions in DCM have not yet been fully understood.Furthermore, a recent study demonstrated that treatment with tauroursodeoxycholic bile acid (TUDCA) reduced adiposity and improved glycemic homeostasis in mice with DCM, highlighting it as the most promising therapeutic strategy for reversing the damage caused by the association of juvenile malnutrition and obesity. . Therefore, with the development of this thematic project we intend to characterize the function of organs and tissues essential to the maintenance of energy metabolism, glycemic homeostasis and cardiovascular and neurological function during DCM and describe the possible molecular and functional mechanisms responsible for the possible therapeutic effects of TUDCA in this condition. nutritional disorder. (AU)